Alexander Wiener Biography (1907-1976)

physician, immunohematologist

Alexander Wiener was a physician who, along with fellow scientist Karl Landsteiner, discovered the Rh factor in blood. He also discovered a number of other antigens (substances in the blood that cause the development of antibodies). The Rh factor is an antigen named after the rhesus monkey, the animal in which it was first discovered. Blood that contains the factor is called Rh-positive, whereas blood that lacks it is labeled Rh-negative. The discovery of the Rh factor led to an understanding of adverse reactions to blood transfusions that occurred inexplicably in some patients even though compatibility of blood type (A, B, AB, and O) in donor and recipient had been observed. The discovery of the Rh factor also brought about an understanding of the possible adverse reactions when an Rh-negative mother carried an Rh-positive fetus. Wiener developed a life-saving method of replacing the damaged blood of new-borninfants who had erythroblastosis fetalis , the infant blood disease that sometimes results from Rh incompatibility. He was also instrumental in getting the results of his research applied to legal issues such as disputed paternity,and to cases involving crimes such as homicide and assault. Author or co-author of more than five hundred scientific articles, he also wrote several books, including what for years was the standard textbook on the subject, Blood Groups and Transfusion. His many awards include the Lasker Award of the American Public Health Association, which he received in 1946, and the Passano Foundation Award, received in 1951.

Alexander Solomon Wiener was born March 16, 1907, in Brooklyn, New York, theson of George Wiener, an attorney who had emigrated from Russia in 1903, andMollie (Zuckerman) Wiener. He attended Brooklyn public schools, graduating from Brooklyn Boys' High School at the age of 15. He was awarded scholarships to attend Cornell University, where he was elected to Phi Beta Kappa in his senior year. Both in high school and in college he pursued an interest in mathematics. In high school he took courses in analytic geometry and calculus andwas a member of the mathematics team and president of the mathematics club. He continued his study of mathematics at Cornell University, and contributed mathematical problems to the American Mathematical Monthly. He majored in biology, however, receiving his A.B. in 1926. He then entered the Long Island College of Medicine (now the SUNY College of Medicine) and was awardedan M.D. in 1930.

While he was in medical school, Wiener began his first research on blood groups at the Jewish Hospital of Brooklyn, where he would also intern from 1930 to 1932 and with which he would be affiliated for his entire professional career. From 1933 to 1935 he served as the head of the Division of Genetics and Biometrics, from 1932 to 1952 as head of the blood transfusion division, and thereafter as attending immunohematologist. From 1949 he was also affiliated with Adelphi Hospital, including three years (1949-1952) as the head of the blood transfusion division. In addition, he began a private medical practice in1932, but three years later he founded Wiener Laboratories, where he limitedhis practice to clinical pathology and blood grouping. In 1938 he joined thefaculty of the Department of Forensic Medicine of New York University Schoolof Medicine, moving up the academic ranks to professor by 1968. In 1938 he also began his long-time association with the Office of the Chief Medical Examiner of New York City. He married Gertrude Rodman in 1932. They had two daughters, Jane Helen and Barbara Rae. Wiener died of leukemia in New York on November 6, 1976.

The background to the discovery of the Rh factor lay in earlier discoveries concerning the nature of blood. In 1901 Karl Landsteiner had distinguished four main human blood groups: A, B, AB, and O. These classifications refer to antigens (substances that produce antibodies) on the surface of the red blood cells. Blood type A contains the A antigen, B contains the B antigen, AB contains both, and O contains neither. However, in the 1920s other blood factors or antigens were discovered--M, N, and P.

In the 1930s Wiener began collaborating with Landsteiner, who was affiliatedwith the Rockefeller Institute for Medical Research in New York. In 1937 Landsteiner and Wiener were studying the M factor in apes and monkeys, focussingon its action as an agglutinogen (its ability to clump red blood cells together). They showed that different anti-M sera (blood sera samples with antibodies opposing the M antigen) produced differing reactions, and concluded that there were at least five distinct M blood factors. This led to further experimentation in which they tested the sera of rabbits immunized with rhesus monkey blood cells. The antibodies produced by rabbit blood in response to rhesusmonkey antigens led them to believe that unknown blood factors might be discovered in human blood by the same method. They began experiments using human blood and the anti-sera from rhesus blood, and thereby discovered a new antigen that they called the Rh factor. The importance of this discovery in transfusions was recognized in 1939 when it was understood that although the first transfusion of Rh-positive blood into an Rh-negative person may be harmless, the sensitization that resulted meant that a second transfusion could cause adangerous hemolytic reaction involving the damage or destruction of red bloodcells.

Wiener then studied the sera from Rh negative patients who had hemolytic transfusion reactions, and the sera from Rh-negative mothers of erythroblastoticbabies. These babies have Rh positive blood, some of which enters the mother's blood, usually shortly before or during birth. The mother's blood forms anantibody to the Rh factor and crosses back to the fetal blood supply. The result is the damage or destruction of the fetal red blood cells containing theRh antigen. He discovered that the expected Rh antibodies often could not befound. He hypothesized that there must be two different forms of Rh antibodies, one that caused the agglutination of cells (which he called bivalent antibodies), the other capable of coating the red blood cells without clumping them (which he called univalent or blocking antibodies). In 1944 and 1945 he developed tests for both types of antibodies.

Wiener noted the fallacy of assuming a one-to-one correspondence between antigens and antibodies. One antigen could produce multiple blood specificities.He soon discovered additional Rh factors that were related to the original one. In the human Rh system (now known as the Rh-Hr system), Wiener and othersestablished as many as 25 different blood factors that form the basis of a large number of blood types.

Wiener's research had many practical implications. It led to an understandingof erythroblastosis fetalis , for which Wiener himself devised (1944-1946) atreatment by means of a complete exchange transfusion replacing the damagedRh-positive blood of the infant with Rh-negative blood. This treatment led toa significant decline in the rate of infant mortality. Knowledge of Rh factors also made blood transfusions far safer. Other implications of Wiener's research derived from the fact that all blood factors are inherited in predictable fashion, and that they combine in a highly specific way in individuals, allowing a sophisticated method of "fingerprinting." Blood factor analysis became important in legal matters (such as establishing paternity), as well as criminal matters, such as the use of blood for identification in homicide and assault. It also facilitated advances in physical anthropology--different groups of people have different proportions of various blood factors, so that tribal movements can sometimes be traced by analysis of blood factor percentagesin populations.

Wiener's research had significant legal implications. He was a member of theAmerican Medical Association legal committee that sponsored blood test laws in all states, and he was the co-author of its 1935 report. He was instrumental in the passage of the New York State law allowing blood tests in disputed paternity cases. He and his father, attorney George Wiener, assisted in drafting a number of laws concerning blood testing that became part of the New YorkState domestic relations, civil, and criminal codes.

Wiener liked playing the piano, going to the movies, and playing cards. He also enjoyed tennis and gulf. In addition, he continued his life-long interestin mathematics and physics by avidly reading in these areas. A member of manyprofessional organizations, he was also an honorary member of the Mystery Writers of America.

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